title: Acute serotonin 2A receptor blocking alters the processing of fearful faces in the orbitofrontal cortex and amygdala.
abstract: BACKGROUND
  The serotonin 2A (5-HT2A) receptor has been implicated in neural-processing of emotionally salient information. To elucidate its role in processing of fear and anger, healthy individuals were studied with functional magnetic resonance imaging (fMRI) after 5-HT2A receptor blockade, while judging the gender of neutral, fearful and angry faces.
  
  
  METHODS
  5-HT2A receptors were blocked with ketanserin to a variable degree across subjects by adjusting the time between ketanserin-infusion and onset of the fMRI protocol. Neocortical 5-HT2A receptor binding in terms of the binding potential (BPp ) was assessed prior to fMRI with (18)F-altanserin positron emission tomography (PET) and subsequently integrated in the fMRI data analysis. Also functional connectivity analysis was employed to evaluate the effect of ketanserin blocking on connectivity.
  
  
  RESULTS
  Compared to a control session, 5-HT2A receptor blockade reduced the neural response to fearful faces in the medial orbitofrontal cortex (OFC), independently of 5-HT2A receptor occupancy or neocortical 5-HT2A receptor BPp . The medial OFC also showed increased functional coupling with the left amygdala during processing of fearful faces depending on the amount of blocked 5-HT2A receptors.
  
  
  CONCLUSIONS
  5-HT2A receptor mediated signaling increases the sensitivity of the OFC to fearful facial expressions and regulates the strength of a negative feedback signal from the OFC to amygdala during processing of fearful faces.
authors.affiliation: 1Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hornboll
authors.forename: Julian
authors.initials: J
authors.lastname: Macoveanu
authors.forename: James
authors.initials: J
authors.lastname: Rowe
authors.forename: Rebecca
authors.initials: R
authors.lastname: Elliott
authors.forename: Olaf B
authors.initials: OB
authors.lastname: Paulson
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000786:Anger; D015283:Citalopram / Q000494:pharmacology; D005149:Facial Expression; D005239:Fear; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D059907:Functional Neuroimaging; D064368:Healthy Volunteers; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010775:Photic Stimulation; D011869:Radioligand Assay; D011930:Reaction Time / Q000187:drug effects; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012737:Sex Factors; D014364:Tryptophan / Q000378:metabolism; D014796:Visual Perception / Q000187:drug effects* / Q000502:physiology
chemical_list: D015283:Citalopram; D007650:Ketanserin; D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan
keywords: Functional magnetic resonance imaging; emotion; fearful faces; ketanserin; positron emission tomography; serotonin; serotonin 2A receptors